This project will examine the effects of substance abuse (SA) on the long-term health morbidity and mortality associated with severe mental illness. The specific aims are to 1) compare a sample of over 850 people with severe mental illness and SA to a sample of over 850 nonabusers with severe mental illness and examine medical comorbidity and mortality over 14 years, specifically for HIV and infectious disease, cardiovascular disease, liver disease, thromboembolic events, diabetes, cardiovascular disease, respiratory disorders, malignant neoplasms and suicide and to 2) examine the effects of demographic (age, race, sex) and clinical variables during initial treatment (severity of illness, severity and duration of substance abuse, weight, blood pressure, glucose, lipids, smoking history and antipsychotic treatment) to the risk of medical morbidity and mortality. This case-cohort design will examine 6 cases per each death for an estimated sample of 1,701 cases with detailed clinical data (243 deaths, 1458 controls). Survival analyses will examine the effects of SA on time to death. These models will be used to estimate unadjusted and age-adjusted risk ratios for total mortality among substance users versus non-users, overall and by diagnosis, and will use interaction terms to explore whether these risk ratios differ by race and gender. Cause-specific mortality and whether SA modifies the prognosis associated with baseline clinical history will be examined. The burdens of psychosis and SA are extremely high. Traditionally these illnesses have been treated and researched as if they occur independently, however approximately half of all people with mental illness have co-occurring SA; a much higher prevalence than the general population. Co-occurring medical disorders and morbidity are increased among people with severe mental illness and substance abuse disorders. However, very little research has been done to compare long-term morbidity and mortality in psychotic patients with and without comorbid SA. Specific morbidities and mortality associated with SA may be preventable if targeted treatments are available for dually diagnosed patients. Specific risk factors and baseline health indices may be indicative of a greater risk and this would be invaluable information to the future of treatment and research for people with severe mental illness who abuse drugs and alcohol as would identifying areas for intervention. Co-occurring medical disorders and morbidity are increased among people with schizophrenia and substance abuse disorders. The burdens associated with both these disorders are extremely high. By better understanding the impact of substance abuse on morbidity and mortality in schizophrenia, specific recommendations for education, policy and future interventions can be built around the outcomes and risk factors defined by the work of this project. This will be an important step for improving the lives of people with schizophrenia. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]